ORGANIC
LETTERS
1
999
Vol. 1, No. 10
579-1581
Synthesis of Nitrogen Heterocycles by
Intramolecular Michael Type of
1
Amination via Reduction of Imines with
Di-n-butyliodotin Hydride (n-Bu SnIH)
2
Toshihiro Suwa, Ikuya Shibata, Keita Nishino, and Akio Baba*
Department of Molecular Chemistry, Graduate School of Engineering,
Osaka UniVersity, 2-1 Yamadaoka, Suita, Osaka 565-0871, Japan
Received August 11, 1999
ABSTRACT
Novel nitrogen heterocycles were prepared by a one-pot procedure involving the reductive amination of the bifunctional substrates containing
an aldehyde and enone groups with di-n-butyliodotin hydride (n-Bu SnIH).
2
3
Intramolecular Michael type amination of ω-amino unsatur-
ated ketones where the amine was created by reductive
amination is a good method for the preparation of nitrogen
heterocycles because enones are effective electrophiles with
reported so far. Another problem is that imines are generally
difficult to isolate because of their instability. This problem
could be solved by reductive amination of the aldehyde
moiety in the presence of an enone group. We have been
developing the unique reactivities of the halogen-substituted
1
amine nucleophiles. However, the method has scarcely been
2
4
5a
used to build nitrogen heterocycles. This may result from
tin hydride systems such as n-Bu SnIH and n-Bu SnClH-
HMPA which promote effective reductions of enones and
imines, respectively. In particular, n-Bu SnClH-HMPA
affords effective reductive aminations. In this Letter, we
describe a facile access to functionalized nitrogen hetero-
2
2
5b,c
the difficulty of chemoselectively generating an amine. If
imine-selective reduction was carried out for a substrate
containing both imine and enone functionalities, the 1,4-
addition of the generated amine would provide nitrogen
heterocycles (Scheme 1).
2
5d
(2) Glanzmann, M.; Karalai, C.; Ostersehlt, B.; Shoen, U.; Frese, C.;
Winterfeldt, E. Tetrahedron Lett. 1982, 38, 2805. (b) Godleski, S.; Heacock,
D. J. J. Org. Chem. 1982, 47, 4820. (c) Parker, K. A.; Cohen, I. D.; Babine,
R. E. Tetrahedron Lett. 1984, 33, 3543. (d) Jeon Y. T.; Lee, C.-P.; Mariano,
P. S. J. Am. Chem. Soc. 1991, 113, 8847. (e) Xu, W.; Zhang, X.-M.;
Mariano, P. S. J. Am. Chem. Soc. 1991, 113, 8863.
Scheme 1
(3) Imine reduction, for example: (a) Hutchins, R. O.; Hutchins, M. K.
ComprehensiVe Organic Synthesis; Trost, B. M., Fleming, I., Eds.;
Pergamon: New York, 1991; Vol. 8, p 25. (b) Lane, C. F. Synthesis 1975,
1
35. (c) Gribble, G. W. Chem. Soc. ReV. 1998, 27, 395.
4) Tin hydride reduction, review. Pereyre, M.; Quintard, J.-P.; Rahm,
A. Tin in Organic Synthesis; Butterworths: London, 1987.
5) (a) Kawakami, T.; Miyatake, M.; Shibata, I.; Baba, A.; Matsuda, H.
J. Org. Chem. 1996, 61, 376. (b) Kawakami, T.; Sugimoto, T.; Shibata, I.;
Baba, A.; Matsuda, H.; N. Sonoda. J. Org. Chem. 1995, 60, 2677. (c)
Shibata, I.; Moriuchi-Kawakami, T.; Tanizawa, D.; Suwa, T.; Sugiyama,
E.; Matsuda H.; Baba, A. J. Org. Chem. 1998, 63, 383. (d) Shibata, I.;
Suwa, T.; Sugiyama, E.; Baba, A. Synlett 1998, 1081.
(
However, as far as we know, no imine-selective reductions
in the presence of reducible enone functions have been
(
(1) Shaefer, M.; Draz, K.; Schwarn, M. StereoselectiVe Synthesis;
Helmchen, G., Hoffmann, R. W., Mulzer, J., Schaumann, E., Eds.;
Thieme: Stuttgart, 1987; Vol. 9, p 5588.
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0.1021/ol990225i CCC: $18.00 © 1999 American Chemical Society
Published on Web 10/15/1999